CN103071187B - Ligament-bone composite scaffold with bionic connection interface and forming method thereof - Google Patents

Abstract

The invention relates to a ligament-bone composite scaffold with a biomimetic connecting interface and a forming method thereof. The forming method comprises the following steps: firstly simulating a natural ligament-bone interface structure and utilizing a rapid forming technology to manufacture a resin negative type of a bone scaffold model with a fiber connecting structure; pouring a bone scaffold material solution into the resin negative type, and performing freeze-drying and high-temperature sintering to manufacture a bone scaffold with an internal communication pipeline and the fiber connecting structure; then primarily connecting ligament fiber with the fiber connecting structure of the bone scaffold, and fixing a die used for manufacturing of a biomimetic interface with a ligament-bone scaffold formed by primary connection; pouring the ligament material composite solution with the bone scaffold material in various changes of concentration into the interface of the ligament and the bone scaffold as secondary connection; and performing freeze-drying and removing the die, so as to obtain the ligament-bone composite scaffold with the biomimetic interface. According to the invention, the transmission of nutrients and metabolites is facilitated, the connecting strength of the ligament-bone composite scaffold is improved, and the ingrowth of cells after implantation is facilitated.

Description

Ligament-bone composite scaffold with bionic connection interface and forming method thereof

technical field

The invention relates to the technical field of biomanufacturing of multi-material and multi-structure bracket composite forming, in particular to a ligament-bone composite bracket with a bionic connection interface and a forming method thereof.

Background technique

Ligaments are the key to maintaining the stability of human joints and normal movement ability, but sports or accidents often lead to non-healing damage or rupture of ligaments, and ligament reconstruction surgery is required clinically to restore their physiological functions. At present, the joint and ligament grafts used in ligament reconstruction surgery, such as autologous ligament, allogeneic ligament, non-degradable artificial ligament, etc., consider their characteristic requirements in terms of strength, while ignoring the interface connection relationship between natural ligament and bone tissue. , medical screws and other means of "mechanical fixation" with the autologous bone, it is difficult to form a firm tissue fusion between the graft and the autologous bone tissue, and the long-term clinical efficacy is poor: either because the fusion tunnel in the autologous bone is enlarged and pulled out, or because of the connection The stress concentration at the place leads to fatigue fracture. Therefore, simulating the characteristics of the natural ligament-bone interface, constructing a bionic ligament-bone tissue scaffold with material and structure transition, and realizing the permanent "physiological fixation" of the ligament and the autogenous bone through the physiological healing of the bone tissue scaffold and the autologous bone, is the current international A problem that the medical profession urgently needs to solve.

Contents of the invention

In order to overcome the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a ligament-bone composite bracket with a bionic connection interface and its forming method. Combined to achieve "physiological fixation" of ligament scaffold and autogenous bone.

A ligament-bone composite scaffold with a bionic connection interface, comprising a ligament scaffold 1 and a bone scaffold 4 connected thereto. The ligament scaffold 1 is woven from biodegradable micro-nano fibers, and the bone scaffold 4 is a porous structure containing fiber connection features. Ceramic structure, the connection interface between the ligament support 1 and the bone support 4 is a porous non-calcified cartilage layer 2 and a calcified cartilage layer 3 simulating the natural ligament-bone interface.

In the ligament scaffold 1 woven by biodegradable micro-nano fibers, the biodegradable micro-nano fibers are polylactic acid fibers, polylactic acid glycolic acid fibers, polycaprolactone fibers, silk, surgical sutures or blends thereof;

Prepare the material solution for making bone scaffold 4, the mass fraction is 40%-70%, the material solution of bone scaffold is composed of bone scaffold material, water solvent, organic monomer, dispersant, crosslinking agent, initiator and catalyst according to 110 -120: 60-80: 6-8: 1-2: 1-1.5: 0.2-0.75: 0.2-0.75 mass ratio mixed composition, bone scaffold material is β-tricalcium phosphate, hydroxyapatite, self-curing bone Cement, calcium silicate or their blends, water solvent is deionized water, organic monomer is acrylamide, methyl-acyloxyethyl trimethyl sodium chloride or adipic acid dihydrazide, dispersant is poly Sodium acrylate or ammonium polyacrylate, the crosslinking agent is N,N-dimethylacrylamide, N,N-diacetonyl acrylamide or dibenzylideneacetonyl acrylamide, the initiator is ammonium persulfate, sodium persulfate Or potassium persulfate, the catalyst is N,N,N,N-tetramethylethylenediamine or N,N-dimethylcyclohexylamine.

A method for forming a ligament-bone composite bracket with a bionic connection interface, comprising the following steps:

1) Use computer 3D aided design software to design a bone scaffold model with internal communication channels and fiber connection structures, as well as a mold that matches the shape of the bone scaffold and is used for bionic interface manufacturing, and design the negative shape of the bone scaffold model through Boolean operations , using rapid prototyping technology to manufacture the resin negative model of the bone scaffold model and the mold for the manufacture of the bionic interface;

2) Prepare the material solution for making the bone scaffold, the mass fraction is 40%-70%, the material solution of the bone scaffold is composed of bone scaffold material, water solvent, organic monomer, dispersant, crosslinking agent, initiator and catalyst according to 110-120: 60-80: 6-8: 1-2: 1-1.5: 0.2-0.75: 0.2-0.75 mass ratio mixed composition, bone scaffold material is β-tricalcium phosphate, hydroxyapatite, self-curing Bone cement, calcium silicate or their blends, the water solvent is deionized water, the organic monomer is acrylamide, methyl-acyloxyethyl trimethyl sodium chloride or adipic acid dihydrazide, and the dispersant is Sodium polyacrylate or ammonium polyacrylate, the cross-linking agent is N,N-dimethylacrylamide, N,N-diacetonyl acrylamide or dibenzylidene acetonyl acrylamide, the initiator is ammonium persulfate, persulfuric acid Sodium or potassium persulfate, the catalyst is N,N,N,N-tetramethylethylenediamine or N,N-dimethylcyclohexylamine, and then the material solution of the bone scaffold is perfused into the resin negative of the bone scaffold model , discharge air bubbles under vacuum conditions, and after the material solution is solidified, put it into a low temperature environment of -20～-80°C for 2-4 hours, and then put it into a vacuum dryer to freeze-dry for 12-36 hours. The body is sintered at a high temperature of 20°C-1550°C to vaporize the negative resin of the bone scaffold model, thereby obtaining a porous ceramic bone scaffold containing a fiber-connected structure;

3) The ligament scaffold is woven from biodegradable micro-nano fibers, and the biodegradable micro-nano fibers are polylactic acid fibers, polylactic acid glycolic acid fibers, polycaprolactone fibers, silk, surgical sutures or their blends;

4) Bundle and connect the fiber connection structure of the ligament support and the bone support to realize the initial connection between the ligament support and the bone support, and then weave the ligament support that has not been bound and connected with the fiber connection structure of the bone support through weaving technology to form the initial connection ligament-bone composite scaffold;

5) Prepare the ligament material solution with the ligament material, water, and dioxane at a mass ratio of 0.5-1.5:0.5-2:6-10. The ligament material is polylactic acid, polylactic acid glycolic acid, polycaprolactone, silk, Surgical sutures or their blends, adding bone scaffold materials of different qualities to the prepared ligament material solution, and uniformly mixing to obtain a composite material with two or more bone scaffold materials with a mass fraction between 5% and 40% solution;

6) Fix the mold used for the manufacture of the bionic interface and the initially connected ligament-bone composite scaffold, and then perfuse the composite material solution layer by layer at the interface of the initially connected ligament-bone composite scaffold, from the end of the bone scaffold to the end of the ligament scaffold, The mass fraction of the bone scaffold material in the composite material solution gradually decreases. Near the end of the bone scaffold, the composite material solution with a high mass fraction of the bone scaffold material is perfused. The height is 0.1-0.5mm, and the mass fraction of the bone scaffold material ranges from 20% to 40%, in the middle part of the connection between the bone scaffold and the ligament scaffold, perfuse the composite material solution with a low mass fraction of the bone scaffold material, the height is 0.1-0.5mm, and the mass fraction of the bone scaffold material ranges from 5% to 20%. The end of the ligament bracket is perfused with the ligament material solution, and the height is 0.1-0.5mm;

7) Pre-freeze the perfused ligament-bone composite scaffold in a low temperature environment of -20～-80°C for 2-4 hours, then freeze-dry it in a vacuum dryer for 12-36 hours, and remove it for the manufacture of bionic interface The mold was used to obtain a ligament-bone composite scaffold with a bionic interface.

The purpose of the present invention is mainly to solve the problem of poor long-term effect of the current ligament reconstruction surgery, and propose a forming method of a ligament-bone composite bracket with a bionic connection interface. The connection between the ligament fiber and the bone support of the present invention is divided into primary connection and secondary connection. The primary connection fixes the ligament fiber and the bone support. The connection strength of the bracket. The secondary connection method is to perfuse the ligament material composite solution with different bone scaffold material concentrations to the ligament-bone interface, which provides a transition of stiffness and avoids the stress concentration problem existing in the direct connection between the ligament and the bone scaffold. The bone bracket and the bone channel can heal physiologically to achieve physiological fixation. The bone scaffold manufactured by the present invention has a connecting pipeline and a bionic interface structure, and the connecting pipeline is helpful for the transmission of nutrients and metabolites. The bionic interface structure also provides an embedded structure for the connection between the ligament fiber and the bone scaffold, which improves the strength of the ligament. - Connection strength of the bone biomimetic scaffold. The bionic interface part of the ligament-bone composite scaffold has a porous structure, which is conducive to the growth of cells after implantation.

Description of drawings

The accompanying drawing is a schematic diagram of a ligament-bone composite scaffold with a bionic connection interface.

Detailed ways

The present invention will be described in detail below in conjunction with examples and accompanying drawings.

Referring to the accompanying drawings, a ligament-bone composite scaffold with a bionic connection interface includes a ligament scaffold 1 and a bone scaffold 4. The ligament scaffold 1 is woven from biodegradable micro-nano fibers, and the bone scaffold 4 is a porous structure containing fiber connection features. Ceramic structure, the connection interface between the ligament support 1 and the bone support 4 is a porous non-calcified cartilage layer 2 and a calcified cartilage layer 3 simulating the natural ligament-bone interface.

A method for forming a ligament-bone composite bracket with a bionic connection interface, comprising the following steps:

1) Use computer 3D aided design software to design a bone scaffold model with internal communication pipes and fiber connection structures, and a mold that matches the shape of the bone scaffold and is used for the manufacture of bionic interfaces. The main body of the bone scaffold is a cylinder. The outer diameter is 11mm, and the diameter of the internal communication pipe is 0.5mm. The inner diameter of the mold used for bionic interface manufacturing is 10mm, the outer diameter is 15mm, and the height is 20mm. The negative shape of the bone scaffold model is designed through Boolean operations, and the rapid prototyping technology is used. Manufactured the resin negative of the bone scaffold model and the mold for the manufacture of the bionic interface;

2) Prepare a material solution for making a bone scaffold with a mass fraction of 58%. The material solution of the bone scaffold consists of β-tricalcium phosphate powder, water solvent deionized water, organic monomer acrylamide, dispersant sodium polyacrylate, Crosslinking agent N,N-dimethylacrylamide, initiator ammonium persulfate and catalyst N,N,N,N-tetramethylethylenediamine according to the mass of 110:70:6:2:1.2:0.36:0.36 Then, pour the material solution of the bone scaffold into the resin negative of the bone scaffold model, and discharge air bubbles under vacuum conditions. After the material solution is solidified, put it in a -20°C refrigerator for 2 hours, and then put it in a vacuum dryer. Freeze-dry for 24 hours, and sinter the dried bone scaffold body at high temperature at 20°C-1150°C to vaporize the negative resin of the bone scaffold model, thereby obtaining a porous ceramic bone scaffold with a fiber-connected structure;

3) The ligament scaffold is woven from biodegradable micro-nano fibers, and the biodegradable micro-nano fibers are polylactic acid fibers, polylactic acid glycolic acid fibers, polycaprolactone fibers, silk, surgical sutures or their blends;

4) Bundle and connect the fiber connection structure of the ligament support and the bone support to realize the initial connection between the ligament support and the bone support, and then weave the ligament support that has not been bound and connected with the fiber connection structure of the bone support through weaving technology to form the initial connection ligament-bone composite scaffold;

5) Prepare a ligament material solution with the ligament material, water, and dioxane at a mass ratio of 1:1:9. The ligament material is polylactic acid. Add bone scaffold materials of different qualities to the prepared ligament material solution and mix them uniformly. Obtaining two kinds of bone scaffold material mass fractions is the composite material solution of 21.4% and 8.3%;

6) Fix the mold used for the manufacture of the bionic interface and the initially connected ligament-bone composite scaffold, and then perfuse the composite material solution layer by layer at the interface of the initially connected ligament-bone composite scaffold, from the end of the bone scaffold to the end of the ligament scaffold, The mass fraction of the bone scaffold material in the composite material solution gradually decreases. Near the end of the bone scaffold, a composite material solution with a mass fraction of the bone scaffold material of 21.4% is perfused to a height of 0.2 mm. Part of the solution enters the porous structure of the bone scaffold and increases the Connection strength, in the middle part of the connection between the bone bracket and the ligament bracket, the composite material solution with a mass fraction of the bone bracket material of 8.3% is perfused with a height of 0.2mm, and at the end near the ligament bracket, the ligament material solution is perfused with a height of 0.2mm;

7) Pre-freeze the perfused ligament-bone composite scaffold for the first time in a low temperature environment of -20°C for 2 hours, then freeze-dry it in a vacuum dryer for 24 hours, remove the mold used for the manufacture of the bionic interface, and obtain a bionic interface ligament-bone composite scaffold.

Claims (3)

1. ligament-bone compound rest with bionical linkage interface, comprise tough belt supporting frame (1) and bone support (4), it is characterized in that: tough belt supporting frame (1) is formed by the braiding of biodegradable micro nanometer fiber, the porous ceramic structure of bone support (4) for comprising fiber connection features, tough belt supporting frame (1) is the non-calcified cartilage layer of porous (2) and calcified cartilage layer (3) of simulating nature ligament-bone interface with bone support (4) linkage interface;

The manufacturing process of ligament-bone compound rest comprises the following steps:

1) utilize Computerized three-dimensional Autocad to design to have the bone support model of interior connecting pipe and fiber syndeton, and the mould mating with bone contoured cradle, manufacture for bionical interface, by Boolean calculation, design the minus of bone support model, utilize rapid shaping technique to produce the resin minus of bone support model and the mould of manufacturing for bionical interface;

2) preparation is for making the material solution of bone support, mass fraction is 40%-70%, the material solution of bone support is by bone holder material, aqueous solvent, organic monomer, dispersant, cross-linking agent, the mass ratio that initiator and catalyst are pressed 110-120:60-80:6-8:1-2:1-1.5:0.2-0.75:0.2-0.75 mixes composition, bone holder material is bata-tricalcium phosphate, hydroxyapatite, self-curing bone cement, calcium silicates or its blend, aqueous solvent is deionized water, organic monomer is acrylamide, methyl-acyl-oxygen ethyl-trimethyl sodium chloride or adipic dihydrazide, dispersant is sodium polyacrylate or ammonium polyacrylate, cross-linking agent is N, N-DMAA, N, N-bis-acetonyl acrylamides or dibenzalacetone base acrylamide, initiator is Ammonium persulfate., sodium peroxydisulfate or potassium peroxydisulfate, catalyst is N, N, N, N-tetramethylethylenediamine or N, N – dimethyl cyclohexyl amine, then to the material solution that pours into bone support in the resin minus of bone support model, under vacuum condition, discharge bubble, after material solution solidifies, put into pre-freeze 2-4h under-20～-80 ℃ of low temperature environments, put into subsequently vacuum drier lyophilization 12-36h, by 20 ℃-1550 ℃ of dried bone support base substrate high temperature sinterings, make the resin minus gasification of bone support model, thereby obtain the porous ceramics bone support that comprises fiber syndeton,

3) by biodegradable micro nanometer fiber, be woven into tough belt supporting frame, biodegradable micro nanometer fiber material is acid fiber by polylactic, polylactic-co-glycolic acid fiber, pla-pcl fiber, silkworm silk, operation suture thread or its blend;

4) tough belt supporting frame and the fiber syndeton of bone support are bundled be connected and realize tough belt supporting frame and be connected with the first of bone support, then by knitting skill, by not bundling with the fiber syndeton of bone support the tough belt supporting frame being connected, weave, form the first ligament-bone compound rest connecting;

5) ligament material, water, dioxane are pressed to the mass ratio preparation ligament material solution of 0.5-1.5:0.5-2:6-10, ligament material is polylactic acid, polylactic-co-glycolic acid, pla-pcl, silkworm silk, operation suture thread or its blend, in the ligament material solution of preparation, add the bone holder material of different quality, after evenly mixing, obtain two kinds and two or more bone holder material mass fraction between 5%～40% composite solution;

6) mould of manufacturing for bionical interface is fixed with the ligament-bone compound rest being connected for the first time, then to ligament-bone compound rest interface of first connection, successively pour into composite solution, from bone bracket end to ligament bracket end, the mass fraction of bone holder material in composite solution successively decreases gradually, in close bone bracket end, the high composite solution of perfusion bone holder material mass fraction, be highly 0.1-0.5mm, the mass fraction scope of bone holder material is 20%～40%, the mid portion being connected with tough belt supporting frame at bone support, the low composite solution of perfusion bone holder material mass fraction, be highly 0.1-0.5mm, the mass fraction scope of bone holder material is 5%～20%, and in close ligament bracket end, perfusion ligament material solution, be highly 0.1-0.5mm,

7) ligament-bone compound rest of the first connection of having poured into is put into pre-freeze 2-4h under-20～-80 ℃ of low temperature environments, put into subsequently vacuum drier lyophilization 12-36h, remove the mould of manufacturing for bionical interface, obtain having ligament-bone compound rest at bionical interface.

2. a kind of ligament-bone compound rest with bionical linkage interface according to claim 1, it is characterized in that: by biodegradable micro nanometer fiber, be woven in tough belt supporting frame (1), biodegradable micro nanometer fiber material is acid fiber by polylactic, polylactic-co-glycolic acid fiber, pla-pcl fiber, silkworm silk, operation suture thread or its blend.

3. a kind of ligament-bone compound rest with bionical linkage interface according to claim 1, is characterized in that: preparation is used for making the material solution of bone support (4), and mass fraction is 40%-70%, and the material solution of bone support is by bone holder material, aqueous solvent, organic monomer, dispersant, cross-linking agent, the mass ratio that initiator and catalyst are pressed 110-120:60-80:6-8:1-2:1-1.5:0.2-0.75:0.2-0.75 mixes composition, and bone holder material is bata-tricalcium phosphate, hydroxyapatite, self-curing bone cement, calcium silicates or its blend, aqueous solvent is deionized water, organic monomer is acrylamide, methyl-acyl-oxygen ethyl-trimethyl sodium chloride or adipic dihydrazide, dispersant is sodium polyacrylate or ammonium polyacrylate, cross-linking agent is N,N-DMAA, N, N-bis-acetonyl acrylamides or dibenzalacetone base acrylamide, initiator is Ammonium persulfate., sodium peroxydisulfate or potassium peroxydisulfate, catalyst is N, N, N, N-tetramethylethylenediamine or N, N – dimethyl cyclohexyl amine.